毒理性
◉ 母乳喂养期间使用总结：拉米夫定在HIV阳性哺乳母亲中进行了充分研究，似乎被她们的母乳喂养婴儿很好地耐受。尚未在因乙型肝炎感染而接受治疗的HIV阴性哺乳母亲中进行研究，但使用的低剂量预计不会对母乳喂养婴儿造成任何严重的不良影响。制造商估计，母乳喂养婴儿的剂量约为2岁以上儿童的婴儿剂量的6%。在美国和其他可以获取清洁水源和负担得起的替代喂养的国家，建议HIV阳性母亲不要母乳喂养她们的婴儿，以避免产后HIV-1感染传播。通过抗逆转录病毒疗法实现并维持病毒抑制，可以将母乳喂养传播风险降低到1%以下，但并非零。在抗逆转录病毒疗法下，病毒载量持续检测不到的HIV感染者如果选择母乳喂养，应在这一决定中得到支持。
一项对现有数据的专家审查得出结论，目前没有理由禁止在母乳喂养期间使用拉米夫定治疗乙型肝炎。一些专业组织指南允许在拉米夫定治疗期间进行母乳喂养，尽管一项指南因缺乏长期安全数据而对此表示警告。长期、低水平婴儿暴露的长期安全数据的缺乏应该与母亲讨论。只要婴儿在出生时接受了乙型肝炎免疫球蛋白和乙型肝炎疫苗，由乙型肝炎感染妇女所生的母乳喂养和配方奶喂养婴儿的感染率没有差异。鼓励患有乙型肝炎的母亲在她们的婴儿接受了这些预防措施后进行母乳喂养。
◉ 对母乳喂养婴儿的影响：一项研究将孕妇随机分配接受齐多夫定单独治疗或高活性抗逆转录病毒疗法（HAART：齐多夫定、拉米夫定和奈韦拉平）以预防母婴传播HIV感染。分娩后，所有婴儿接受了一个月的齐多夫定预防治疗；一些婴儿接受了母乳喂养，而其他婴儿接受了配方奶喂养。在1个月大时，HAART暴露组的婴儿中性粒细胞减少的比例高于未暴露组（分别为15.9%和3.7%）。血液学毒性是短暂的且无症状的。在产后2到6个月期间，母乳喂养和配方奶喂养婴儿之间的血液学毒性没有差异。母乳喂养和配方奶喂养婴儿之间的肝毒性没有统计学差异。
24名由HIV阳性母亲母乳喂养的婴儿在6个月大时发展为HIV感染。其中6名婴儿可能因母乳中拉米夫定亚治疗水平而选择了突变。
一名HIV阳性母亲每天服用一次含有多替拉韦50毫克、硫酸阿巴卡韦600毫克和拉米夫定300毫克（特鲁迈克）的复方片剂。她的婴儿大约30周内接受了纯母乳喂养，另外20周内接受了部分母乳喂养。没有观察到明显的不良反应。
一名母亲在分娩前33天和分娩后8天共服用拉米夫定治疗慢性乙型肝炎。她的婴儿接受了母乳喂养（程度未说明）。在3个月大时，婴儿死亡，死亡归因于婴儿猝死综合症。死亡不太可能与拉米夫定有关。
◉ 对泌乳和母乳的影响：在接受高活性抗逆转录病毒疗法的男性中报告了男性乳房发育。男性乳房发育最初是单侧的，但在大约一半的病例中进展为双侧。没有观察到血清催乳素的变化，自发解决通常在一年内发生，即使继续使用该方案。一些病例报告和体外研究表明，蛋白酶抑制剂可能在上一些男性患者中引起高催乳素血症和乳汁分泌过多，尽管这一点存在争议。这些发现与哺乳母亲的相关性尚不清楚。在已建立泌乳的母亲中，催乳素水平可能不会影响她的哺乳能力。
◉ Summary of Use during Lactation:Lamivudine has been well studied in HIV-positive nursing mothers and appears to be well tolerated by their breastfed infants. It has not been studied in HIV-negative nursing mothers being treated for hepatitis B infection, but the low doses used would not be expected to cause any serious adverse effects in breastfed infants. The manufacturer estimates that a breastfed infant's dose would be about 6% of the infant dose for children over 2 years of age. In the US and other countries where access to clean water and affordable replacement feeding are available, it is recommended that mothers living with HIV not breastfeed their infants to avoid postnatal transmission of HIV-1 infection. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision.
An expert review of available data concluded that there is currently no justification for contraindicating the use of lamivudine for hepatitis B therapy during breastfeeding. Some professional organization guidelines allow breastfeeding during lamivudine therapy, although one guideline cautions against it because of a lack of long-term safety data. The lack of long-term safety data with long-term, low-level infant exposure should be discussed with the mother. No differences exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures.
◉ Effects in Breastfed Infants:A study assigned pregnant women to zidovudine alone or highly active antiretroviral therapy (HAART: zidovudine, lamivudine and nevirapine) to prevent maternal-to-child transmission of HIV infection. After delivery, all infants received one month of zidovudine prophylaxis; some infants were breastfed and others were formula fed. A higher percentage of infants in the HAART-exposed group had neutropenia than those in the unexposed group at 1 month of age (15.9% and 3.7%, respectively). Hematologic toxicity was transient and asymptomatic. From 2 to 6 months postpartum, no differences in hematologic toxicity were seen between breastfed and formula-fed infants. No statistical difference in hepatic toxicity was seen between the breastfed and formula-fed infants.
Twenty-four infants who were breastfed by HIV-positive mothers developed HIV infection by 6 months of age. Six of these infants had a mutation that might have been selected for by subtherapeutic levels of lamivudine in breastmilk.
An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted.
One mother took lamivudine for 33 days, 25 before birth and eight days postpartum for chronic hepatitis B infection. Her infant was breastfed (extent not stated). At three months of age, the infant died with the death attributed to sudden infant death syndrome. The death was unlikely to be related to lamivudine.
◉ Effects on Lactation and Breastmilk:Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
来源:Drugs and Lactation Database (LactMed)
